ABSTRACT

Immune checkpoint inhibitors (ICI) have transformed the therapeutic landscape in oncology. However, ICI can induce uncommon life-threatening autoimmune T-cell-mediated myotoxicities, including myocarditis and myositis. The thymus plays a critical role in T cell maturation. Here we demonstrate that thymic alterations are associated with increased incidence and severity of ICI myotoxicities. First, using the international pharmacovigilance database VigiBase, the Assistance Publique Hôpitaux de Paris-Sorbonne University data warehouse (Paris, France) and a meta-analysis of clinical trials, we show that ICI treatment of thymic epithelial tumors (TET, and particularly thymoma) was more frequently associated with ICI myotoxicities than other ICI-treated cancers. Second, in an international ICI myocarditis registry, we established that myocarditis occurred earlier after ICI initiation in patients with TET (including active or prior history of TET) compared to other cancers and was more severe in terms of life-threatening arrythmias and concurrent myositis, leading to respiratory muscle failure and death. Lastly, we show that presence of anti-acetylcholine-receptor antibodies (a biological proxy of thymic-associated autoimmunity) was more prevalent in patients with ICI myocarditis than in ICI-treated control patients. Altogether, our results highlight that thymic alterations are associated with incidence and seriousness of ICI myotoxicities. Clinico-radio-biological workup evaluating the thymus may help in predicting ICI myotoxicities.

PMID:37884625 | DOI:10.1038/s41591-023-02591-2

15:16

PubMed articles on: Cancer & VTE/PE

Evaluating the effect of immune checkpoint inhibitors on venous thromboembolism in non-small cell lung cancer patients

Expert Rev Hematol. 2023 Oct 26:1-8. doi: 10.1080/17474086.2023.2276209. Online ahead of print.

ABSTRACT

OBJECTIVE: Currently, immune checkpoint inhibitors (ICIs) therapy is one of the main methods of treatment in non-small cell lung cancer (NSCLC). This study aimed to explore the risk factors of VTE and evaluate the effect of ICIs on VTE in patients with NSCLC.

RESEARCH DESIGN AND METHODS: We retrospectively studied patients with NSCLC who were divided into VTE group and without VTE (Non-VTE) group. We identified the risk factors of VTE in NSCLC patients and evaluated the effect of ICIs on VTE in NSCLC patients.

RESULTS: We found that clinical stage III-IV (P = 0.015) and Khorana score (KS) ≥ 2 (P = 0.047) were independent risk factors for the occurrence of VTE in NSCLC, and treatment with ICIs reduced the risk of VTE occurrence (P = 0.028). There were no differences of survival rates in the 12-month (P = 0.449), 24-month (P = 0.412), or 36-month (P = 0.315) between the VTE and non-VTE groups. History of anti-angiogenic therapy (P = 0.033) and chronic obstructive pulmonary disease (COPD) (P = 0.046) were independent risk factors for VTE in NSCLC patients who were treated with ICIs.

CONCLUSION: This study suggests that we should strengthen anticoagulant therapy when using ICIs for NSCLC patients with a history of anti-angiogenic therapy and COPD.

PMID:37883026 | DOI:10.1080/17474086.2023.2276209

15:16

PubMed articles on: Cancer & VTE/PE

Hospital-Acquired Venous Thromboembolism and Invasive Mechanical Ventilation: A Report From the Children's Hospital Acquired Thrombosis Consortium

Pediatr Crit Care Med. 2023 Oct 26. doi: 10.1097/PCC.0000000000003383. Online ahead of print.